“This paper describes mice harboring a GFP-Foxp3 “knock-in” reporter allele.”

This paper is built upon initial observations from our lab and other labs—Hori et al., Science 299(5609):1057-61, Feb 14, 2003; Fontenot et al., Nat. Immunol. 4(4):330-6, Apr, 2003; Khattri et al., Nat. Immunol. 4(4):337-42, Apr, 2003. This paper firmly establishes the forkhead transcription factor Foxp3 as the "master regulator" of the regulatory T cell lineage. Together these papers establish a molecular basis for the phenomenon of dominant immunological tolerance.

This paper reports the generation and analysis of mice expressing a chimeric Green Fluorescent Protein (GFP)-Foxp3 fusion protein from a "knock-in" reporter allele. In these mice, all Foxp3-expressing cells are identified by GFP fluorescence.

Using this system, regulatory T cells are, for the first time, unambiguously differentiated from effector T cells and basic aspects of their development and function are defined.

This allele opens the door for functional analysis of regulatory T cells in settings of immune pathology, including autoimmunity, chronic infection, transplantation, and tumorigenesis.

Most importantly, this study provides unambiguous proof that deficiency in regulatory T cells is a cause of fatal aggressive autoimmune pathology in mice and humans. These results demonstrate the vital role of Foxp3-mediated dominant tolerance for the immune homeostasis.

This paper describes mice harboring a GFP-Foxp3 "knock-in" reporter allele. Using homologous recombination in ES cells, the cDNA encoding GFP was inserted in-frame into the first coding exon of Foxp3. The allele encodes a GFP-Foxp3 fusion protein from the endogenous Foxp3 locus. These mice are an invaluable tool for studying regulatory T cell biology.

This paper describes a central role for the transcription factor Foxp3 in the development and function of regulatory T cells. Regulatory T cells are critical for the maintenance of immune system homeostasis and tolerance to self.

There is a great clinical interest in regulatory T cells due to evidence from experimental animal models demonstrating that the immunosuppressive potential of these cells can be harnessed therapeutically to treat autoimmune diseases and facilitate transplantation tolerance or specifically eliminated to potentiate cancer immunotherapy.